Diabetes is one of the most common health concerns worldwide. Treatment of diabetes requires frequent and accurate monitoring of blood glucose concentrations. Blood glucose is one of the most important blood analytes, and some sources refer to blood glucose concentration as the “next vital sign”. Optimized insulin therapy facilitated by frequent to continuous accurate monitoring of blood glucose concentration coupled with metabolic control is proposed as one way to reduce the risk of chronic diabetes symptoms.
Although not as well appreciated or understood, the stress of traumatic events such as severe physical injury, heart attack, and surgery, can elevate blood glucose concentration in people who did not have diabetes before the traumatic event. This spontaneous elevation is referred to as “stress induce hyperglycemia”. Multiple reports have shown a correlation between stress-induced hyperglycemia and increased morbidity and mortality in intensive care units (ICUs). In 2001, it was reported that maintaining blood glucose within a normal range of 80-110 mg/dL (4.4-6.1 mM), often referred to as tight glycemic control (TGC), reduces surgical ICU mortality by 42% (van den Berghe et al., N Engl J Med. 2001 Nov. 8; 345(19):1359). It was demonstrated in the same report that “intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care.” In 2006, it was reported that intensive insulin therapy significantly reduced morbidity among all patients in medical ICUs (van den Berghe et al., N Engl J Med. 2006, Feb. 2; 354 (5): 449). These benefits have led ICUs to implement TGC protocols, which in turn has led to interest in automated continuous glucose monitors that can provide continuous or nearly continuous monitoring of blood glucose levels.
Intense research efforts have focused on development of continuous glucose sensing technologies (Koschinsky et al., Diabetes/Metabolism Res. Rev. 2001, 17, 113-123.). To meet the requirements for continuous glucose monitoring, a sensor must exhibit high precision, accuracy, sensitivity and stability. From a clinical standpoint, the calibration requirements, availability of results, longevity, and robustness should all be considered when assessing the applicability of a sensor. A motivation for linearly responsive sensors includes their ease of calibration, and the potential for high precision, accuracy, little or no hysteresis and consistent sensitivity over the entire sensing range associated with blood glucose levels. Fast response kinetics is a desirable attribute for continuous glucose monitoring to observe blood glucose fluctuations. High stability of the material is also required to ensure consistent sensor performance during a patient's stay in the ICU, which is typically three days.
Many types of technology have been applied to blood glucose measurement, but none has been successfully developed such that it provides a sensor that satisfies the requirements for accurate and continuous glucose monitoring, particularly of patients in hospital intensive care units. Accordingly, there is a need for new and effective continuous glucose measurement technologies. The glucose sensing technology should provide high precision, accuracy, sensitivity, and stability, fast response kinetics and little or no hysteresis.